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the psychomotor and psychometric effects induced by ethanol in these same subjects when they were not receiving venlafaxine. Cimetidine Concomitant administration of cimetidine and venlafaxine in a steady-state study for both drugs resulted in inhibition of first-pass metabolism of venlafaxine in 18 healthy subjects. The oral clearance of venlafaxine was reduced by about 43%, and the exposure (AUC) and maximum concentration (Cmax) of the drug were increased by about 60%.

However, coadministration of cimetidine had no apparent effect on the pharmacokinetics of ODV, which is present in much greater quantity in the circulation than venlafaxine. The overall pharmacological activity of venlafaxine plus ODV is expected to increase only slightly, and no dosage adjustment should be necessary for most normal adults. However, for patients with pre-existing hypertension, and for elderly patients or patients with hepatic dysfunction, the interaction associated with the concomitant use of venlafaxine and cimetidine is not known and potentially could be more pronounced. Therefore, caution is advised with such patients.



Diazepam

Under steady-state conditions for venlafaxine administered at 150 mg/ day, a single 10 mg dose of diazepam did not appear to affect the pharmacokinetics of either venlafaxine or ODV in 18 healthy male subjects. Venlafaxine also did not have any effect on the pharmacokinetics of diazepam or its active metabolite, desmethyldiazepam, or affect the psychomotor and psychometric effects induced by diazepam.

Haloperidol Venlafaxine administered under steady-state conditions at 150 mg/ day in 24 healthy subjects decreased total oral-dose clearance (Cl/ F) of a single 2 mg dose of haloperidol by 42 ,which resulted in a 70 increase in haloperidol AUC. In addition, the haloperidol Cmax increased 88 when coadministered with venlafaxine, but the haloperidol elimination half-life (t1/ 2) was unchanged. The mechanism explaining this finding is unknown. Lithium The steady-state pharmacokinetics of venlafaxine administered at 150 mg/ day were not affected when a single 600 mg oral dose of lithium was administered to 12 healthy male subjects. ODV also was unaffected. Venlafaxine had no effect on the pharmacokinetics of lithium (see also


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